Glycosylated hemoglobin (HbA1c) targets for patients with chronic kidney disease (CKD) and type 2 diabetes remain controversial. To evaluate whether baseline HbA
1c
and HbA
1c
trajectories are ...associated with the risk of end-stage kidney disease (ESKD) and all-cause mortality, we recruited adult patients with CKD and type 2 diabetes from a “Pre-ESKD Program” at a medical center in Taiwan from 2003 to 2017. Group-based trajectory modeling was performed to identify distinct patient groups that contained patients with similar longitudinal HbA1c patterns. Cox proportional hazard models were used to estimate hazard ratios (HRs) of ESKD and mortality associated with baseline HbA
1c
levels and HbA
1c
trajectories. In the analysis related to baseline HbA
1c
(
n
= 4543), the adjusted HRs 95% confidence interval (CI) of all-cause mortality were 1.06 (0.95–1.18) and 1.25 (95% CI, 1.07–1.46) in patients with an HbA
1c
level of 7%–9% (53–75 mmol/mol) and >9% (>75 mmol/mol), respectively, as compared with those with an HbA1c level < 7% (<53 mmol/mol). In the trajectory analysis
(n
= 2692), three distinct longitudinal HbA
1c
trajectories were identified: nearly optimal (55.9%), moderate to stable (34.2%), and poor control (9.9%). Compared with the “nearly optimal” HbA
1c
trajectory group, the “moderate-to-stable” group did not have significantly higher mortality, but the “poorly controlled” group had 35% higher risk of mortality (adjusted HR = 1.35, 95% CI = 1.06–1.71). Neither baseline levels of HbA
1c
nor trajectories were associated with ESKD risk. In conclusion, in patients with CKD and type 2 diabetes, poor glycemic control was associated with an elevated risk of mortality but not associated with a risk of progression to ESKD.
Bangladesh is one of the most disaster-prone countries in the world. In particular, its riverine-island (char) dwellers face continuous riverbank erosion, frequent flooding, and other adverse effects ...of climate change that increase their vulnerability. This paper aims to assess the livelihood vulnerability of riverine communities by applying the Intergovernmental Panel on Climate Change (IPCC) vulnerability framework and the livelihood vulnerability index (LVI). Results indicate substantial variation in the vulnerability of char dwellers based on mainland proximity. The main drivers of livelihood vulnerability are char-dweller adaptation strategies and access to food and health services. The study further reveals that riverbank erosion, frequent flood inundation, and lack of employment and access to basic public services are the major social and natural drivers of livelihood vulnerability. Char-based policy focusing on short- and long-term strategy is required to reduce livelihood vulnerability and enhance char-dweller resilience.
Hypertension is known to be related to obesity and both are the major factors for cardiovascular diseases. The relationship between body composition and blood pressure (BP) are discussed recently. ...Our study aims to evaluate the association between waist circumference (WC) and appendicular muscle mass (AMM) in relation to BP among the community‐dwelling elderly population.
Total 3739 patients (1600 males and 2139 females) were recruited in a series of community‐based surveys that were conducted among the elderly population in Taiwan from 2017 to 2019. We collected data on anthropometric characteristics, handgrip strength, and BP using standard methods. AMM was calculated with an equation. History of chronic disease and lifestyle profiles were collected using questionnaires.
The group with high AMM to body weight ratio (AMMW) showed lower systolic BP (SBP) (136.8 ± 19.1 to 140.6 ± 17.0 for males; 137.8 ± 18.3 to 142.7 ± 17.5 for females, both P < .001). Among central obese persons those with higher AMMW ratio had lower SBP. In the final model, AMMW in percentage is negatively associated to SBP (β = −0.641 in male, −0.780 in female, both P < .01). In other words, every 10% increase in AMMW is associated with decrease of SBP 6.41 mmHg in male and 7.80 mmHg in female.
Obesity and central obesity were positively associated with BP. The AMMW ratio was negatively associated with HTN and with a protective effect on BP even among the central obese. Health promotion programs to increase physical training may prevent hypertension among the elderly in Taiwan.
The CpXRh(III)-catalyzed asymmetric cascade C-H coupling/intramolecular cyclization of azomethine imines with propargyl carbonates has been developed, affording a variety of chiral tetracyclic ...indenopyrazolopyrazolone frameworks with good substrate/functional group tolerance and enantioselectivity (up to 97:3 er). Combined experimental studies and DFT calculations revealed the Rh(III)-catalyzed stepwise annulation process and clarified the synergy coordination mode of dual directing groups in tuning the selectivity.
By virtue of the azomethine imine moiety and the -OBoc group as synergistic dual directing groups, the enantioselective Rh(III)-catalyzed C-H allenylation/intramolecular 3 + 2 dipolar cycloaddition sequence has been realized for the assembly of tetracyclic indenopyrazolopyrazolone frameworks with specific regioselectivity. Display omitted
Integrating Software-Defined Networking (SDN) and Edge Computing (EC) technologies becomes a promising approach to harness enormous data traffic in the Internet. Recent studies examined the Quality ...of Service (QoS) based routing paradigms for different data applications such as IoT, heterogeneous networks, and 5G network slicing in such integrated networks. In this paper, our study formulates the QoS-specific routing optimization as a minimum-cost resource allocation problem, while multi-dimensional factors of bandwidth cost, latency, and packet loss are jointly considered. Since we use the fittingness factor to help the problem solving, we propose a path selection scheme based on the measure of fittingness factor, briefly named as FitPath. The FitPath scheme can appropriately adjust network resources to maintain delivery time against various service requirements of user demands. Simulation results show that the FitPath scheme can perform better than the Open Shortest Path First (OSPF) and Greedy heuristic schemes in terms of the total of link costs, delivery latency, and packet loss rate under both of normal and heavy data traffic experiments. The effects by the FitPath scheme can be further enhanced with the top-<inline-formula> <tex-math notation="LaTeX">B </tex-math></inline-formula>% path selection policy in integrated network environments.
Ploidy variation is a cancer hallmark and is frequently associated with poor prognosis in high-grade cancers. Using a Drosophila solid-tumor model where oncogenic Notch drives tumorigenesis in a ...transition-zone microenvironment in the salivary gland imaginal ring, we find that the tumor-initiating cells normally undergo endoreplication to become polyploid. Upregulation of Notch signaling, however, induces these polyploid transition-zone cells to re-enter mitosis and undergo tumorigenesis. Growth and progression of the transition-zone tumor are fueled by a combination of polyploid mitosis, endoreplication, and depolyploidization. Both polyploid mitosis and depolyploidization are error prone, resulting in chromosomal copy-number variation and polyaneuploidy. Comparative RNA-seq and epistasis analysis reveal that the DNA-damage response genes, also active during meiosis, are upregulated in these tumors and are required for the ploidy-reduction division. Together, these findings suggest that polyploidy and associated cell-cycle variants are critical for increased tumor-cell heterogeneity and genome instability during cancer progression.
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•Active Notch induces polyploid imaginal ring cells to re-enter mitosis•Polyploid mitosis, endoreplication, and depolyploidization together promote tumor growth•Ploidy-reduction division depends on genes involved in DNA-damage response and repair•Tumor progression correlates with increased ploidy heterogeneity and polyaneuploidy
Wang et al. show that polyploidy is key to tumor initiation and progression in a Notch-induced Drosophila tumor model. Polyploid mitosis, endoreplication, and depolyploidization promote genomic instability and polyaneuploidy. The ploidy-reduction division depends on genes involved in DNA-damage response, which are also active in meiosis.
Breast cancer (BC) is the most frequent malignancy and is ranking the leading cause of cancer-related death among women worldwide. At present, BC is still an intricate challenge confronted with high ...invasion, metastasis, drug resistance, and recurrence rate. Exosomes are membrane-enclosed extracellular vesicles with the lipid bilayer and recently have been confirmed as significant mediators of tumor cells to communicate with surrounding cells in the tumor microenvironment. As very important orchestrators, non-coding RNAs (ncRNAs) are aberrantly expressed and participate in regulating gene expression in multiple human cancers, while the most reported ncRNAs within exosomes in BC are microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Notably, ncRNAs containing exosomes are novel frontiers to shape malignant behaviors in recipient BC cells such as angiogenesis, immunoregulation, proliferation, and migration. It means that tumor-derived ncRNAs-containing exosomes are pluripotent carriers with intriguing and elaborate roles in BC progression
via
complex mechanisms. The ncRNAs in exosomes are usually excavated based on specific de-regulated expression verified by RNA sequencing, bioinformatic analyses, and PCR experiments. Here, this article will elucidate the recent existing research on the functions and mechanisms of tumor-derived exosomal miRNA, lncRNA, circRNA in BC, especially in BC cell proliferation, metastasis, immunoregulation, and drug resistance. Moreover, these tumor-derived exosomal ncRNAs that existed in blood samples are proved to be excellent diagnostic biomarkers for improving diagnosis and prognosis. The in-depth understanding of tumor-derived exosomal ncRNAs in BC will provide further insights for elucidating the BC oncogenesis and progress and exploring novel therapeutic strategies for combating BC.
Silica ceramic cores have played an important part in the manufacture of hollow blades due to their excellent chemical stability and moderate high-temperature mechanical properties. In this study, ...silica-based ceramics were prepared with Al
2
O
3
addition by stereolithography, and the influence of Al
2
O
3
content on mechanical properties of the silica-based ceramics was investigated. The Al
2
O
3
in silica-based ceramics can improve the mechanical properties by playing a role as a seed for the crystallization of fused silica into cristobalite. As a result, with the increase of Al
2
O
3
content, the linear shrinkage of the silica-based ceramics first decreased and then increased, while the room-temperature flexural strength and the high-temperature flexural strength first increased and then decreased. As the Al
2
O
3
content increased to 1.0 vol%, the linear shrinkage was reduced to 1.64% because of the blocked viscous flow caused by Al
2
O
3
. Meanwhile, the room-temperature flexural strength and the high-temperature flexural strength were improved to 20.38 and 21.43 MPa with 1.0 vol% Al
2
O
3
, respectively, due to the increased α-cristobalite and β-cristobalite content. Therefore, using the optimal content of Al
2
O
3
in silica-based ceramics can provide excellent mechanical properties, which are suitable for the application of ceramic cores in the manufacturing of hollow blades.
Background & Aims Little is known about functions of microRNA (miR) passenger strands (miR*) or their roles in tumor development or progression. We screened for miRs and miR* with levels that were ...altered in metastatic colorectal cancer (CRC) cells and human tumor samples and investigated their targets and effects on cell function and tumor progression in mice. Methods We performed array-based profile analysis to identify miRs with levels that were increased more than 2-fold in metastatic (SW620) CRC cells compared with nonmetastatic (SW480) cells. Quantitative polymerase chain reaction and in situ hybridization analyses were used to measure miRNA levels in CRC cell lines and human tumor samples. We used miRNA duplex mimics or inhibitors to increase and decrease levels of miRNA in CRC cells and assessed their activities and ability to form metastatic xenograft tumors in nude mice. Results Levels of miR-221* and miR-224 were reduced in metastatic compared with nonmetastatic CRC cells; levels in human tumor samples correlated inversely with tumor stage and metastasis to lymph nodes as well as patient survival times. SW480 cells transfected with miR-221* or miR-224 inhibitors had increased motility in vitro compared with SW480 control cells and formed larger, more metastatic tumors when injected into mice. SW620 cells transfected with miR-221* or miR-224 mimics had reduced migration and motility in vitro and formed smaller tumors with fewer metastases in mice compared with control SW620 cells. We identified the 3′ untranslated region of MBD2 messenger RNA as a target of miR-221* and miR-224. MBD2 silences the gene encoding maspin, a suppressor of metastasis. In CRC cells, we found that miR-221* and miR-224 increase the expression of maspin through MBD2 down-regulation. Conclusions In metastatic CRC cells, reduced levels of miR-221* and miR-224 increase levels of MBD2, thereby decreasing expression of the metastasis suppressor maspin. Increased activities of miR-221* and miR-224 reduce growth and metastasis of CRC xenograft tumors in mice; these miRs might be developed as therapeutic reagents or biomarkers of CRC progression.
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